Caleb A. Lareau
Broad Institute
GeneGeneticsComputational biologyChromatinBiology
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Publications 54
#1John P. Ray (Broad Institute)H-Index: 3
#2Carl G. de Boer (Broad Institute)H-Index: 6
Last. Drew T Bergman (Broad Institute)H-Index: 1
view all 16 authors...
Genome-wide association studies have associated thousands of genetic variants with complex traits and diseases, but pinpointing the causal variant(s) among those in tight linkage disequilibrium with each associated variant remains a major challenge. Here, we use seven experimental assays to characterize all common variants at the multiple disease-associated TNFAIP3 locus in five disease-relevant immune cell lines, based on a set of features related to regulatory potential. Trait/disease-associat...
#1Anindita Basak (MIT: Massachusetts Institute of Technology)H-Index: 2
#2Mathias Munschauer (MIT: Massachusetts Institute of Technology)H-Index: 12
Last. Vijay G. Sankaran (MIT: Massachusetts Institute of Technology)H-Index: 33
view all 21 authors...
Increased production of fetal hemoglobin (HbF) can ameliorate the severity of sickle cell disease and β-thalassemia1. BCL11A represses the genes encoding HbF and regulates human hemoglobin switching through variation in its expression during development2–7. However, the mechanisms underlying the developmental expression of BCL11A remain mysterious. Here we show that BCL11A is regulated at the level of messenger RNA (mRNA) translation during human hematopoietic development. Despite decreased BCL1...
1 CitationsSource
#1Caleb A. LareauH-Index: 14
#2Leif S. Ludwig (Broad Institute)H-Index: 10
Last. Vijay G. Sankaran (Broad Institute)H-Index: 33
view all 3 authors...
Our ability to track cellular dynamics in humans over time in vivo has been limited. Here, we demonstrate how somatic mutations in mitochondrial DNA (mtDNA) can be used to longitudinally track the dynamic output of hematopoietic stem and progenitor cells in humans. Over the course of 3 years of blood sampling in a single individual, our analyses reveal somatic mtDNA sequence variation and evolution reminiscent of models of hematopoiesis established by genetic labeling approaches. Furthermore, we...
#1Huidong ChenH-Index: 5
#2Caleb A. Lareau (Broad Institute)H-Index: 14
Last. Luca PinelloH-Index: 22
view all 9 authors...
Recent innovations in single-cell Assay for Transposase Accessible Chromatin using sequencing (scATAC-seq) enable profiling of the epigenetic landscape of thousands of individual cells. scATAC-seq data analysis presents unique methodological challenges. scATAC-seq experiments sample DNA, which, due to low copy numbers (diploid in humans), lead to inherent data sparsity (1–10% of peaks detected per cell) compared to transcriptomic (scRNA-seq) data (10–45% of expressed genes detected per cell). Su...
5 CitationsSource
#1Caleb A. Lareau (Harvard University)H-Index: 14
#2Sai Ma (MIT: Massachusetts Institute of Technology)H-Index: 1
Last. Jason D. Buenrostro (Harvard University)H-Index: 23
view all 4 authors...
A widespread assumption for single-cell analyses specifies that one cell9s nucleic acids are predominantly captured by one oligonucleotide barcode. However, we show that ~13-21% of cell barcodes from the 10x Chromium scATAC-seq assay may have been derived from a droplet with more than one oligonucleotide sequence, which we call "barcode multiplets". We demonstrate that barcode multiplets can be derived from at least two different sources. First, we confirm that ~4% of droplets from the 10x platf...
1 CitationsSource
#1Erik L. Bao (Harvard University)H-Index: 4
#2Satish K. Nandakumar (Broad Institute)H-Index: 5
Last. Vijay G. Sankaran (Boston Children's Hospital)H-Index: 33
view all 33 authors...
Myeloproliferative neoplasms (MPNs) are blood cancers characterized by excessive production of mature myeloid cells that result from the acquisition of somatic driver mutations in hematopoietic stem cells (HSCs). While substantial progress has been made to define the causal somatic mutation profile for MPNs, epidemiologic studies indicate a significant heritable component for the disease that is among the highest known for all cancers. However, only a limited set of genetic risk loci have been i...
#1Julian Grünewald (Harvard University)H-Index: 1
#1Julian Grünewald (Harvard University)H-Index: 2
Last. J. Keith Joung (Harvard University)H-Index: 62
view all 7 authors...
Cytosine or adenine base editors (CBEs or ABEs) can introduce specific DNA C-to-T or A-to-G alterations1–4. However, we recently demonstrated that they can also induce transcriptome-wide guide-RNA-independent editing of RNA bases5, and created selective curbing of unwanted RNA editing (SECURE)-BE3 variants that have reduced unwanted RNA-editing activity5. Here we describe structure-guided engineering of SECURE-ABE variants with reduced off-target RNA-editing activity and comparable on-target DNA...
14 CitationsSource
#1Charles P. Fulco (Broad Institute)H-Index: 6
#2Joseph Nasser (Broad Institute)H-Index: 3
Last. Jesse M. Engreitz (Broad Institute)H-Index: 22
view all 19 authors...
Enhancer elements in the human genome control how genes are expressed in specific cell types and harbor thousands of genetic variants that influence risk for common diseases1–4. Yet, we still do not know how enhancers regulate specific genes, and we lack general rules to predict enhancer–gene connections across cell types5,6. We developed an experimental approach, CRISPRi-FlowFISH, to perturb enhancers in the genome, and we applied it to test >3,500 potential enhancer–gene connections for 30 gen...
23 CitationsSource
#1Thais S. SabedotH-Index: 6
#2Seth H. CasselH-Index: 4
view all 8 authors...
#1Caleb A. Lareau (Broad Institute)H-Index: 14
#2Fabiana M. Duarte (Broad Institute)H-Index: 5
Last. Jason D. Buenrostro (Broad Institute)H-Index: 23
view all 11 authors...
Recent technical advancements have facilitated the mapping of epigenomes at single-cell resolution; however, the throughput and quality of these methods have limited their widespread adoption. Here we describe a high-quality (105 nuclear fragments per cell) droplet-microfluidics-based method for single-cell profiling of chromatin accessibility. We use this approach, named ‘droplet single-cell assay for transposase-accessible chromatin using sequencing’ (dscATAC-seq), to assay 46,653 cells for th...
10 CitationsSource